The heart is an organ with the unique function of continually repeated contraction and relaxation. Myocardial cells, which are the main components of the heart, maintain division potential after differentiation, and keep actively dividing and proliferating during the prenatal period. However, they lose their division potential at the time of birth, and thereafter the growth of the heart is dependent on the growth in size of individual myocardial cells (physiological hypertrophy).
There are some cases wherein the heart responds to various stimuli such as hypertension thereby growing in size more than it would physiologically, and this is called in general cardiac hypertrophy. Cardiac hypertrophy is a compensatory mechanism having a limitation and does not reduce contraction function of the heart in itself. However, a high hypertrophy exceeding the limitation causes biochemical changes in the myocardial cells, so that the heart suffers contraction dysfunction (heart failure).
There have been already some reports on the onset mechanism of heart failure. For example, Hasegawa et al. reported that GATA transcription factors played an important role in intracellular signal transduction at the onset of heart failure (Hasegawa K et al.: Circulation 1997; 96:3943-3953). Morimoto et al. reported that among the GATA transcription factors, GATA-5 played a particularly important role (Morimoto T et al.: J. Biol. Chem. 1999; 274:12811-12818). Further, Iwanaga et al. reported that the expression enhancement of endothelin-1 in cardiac muscle played an important role in the development from compensatory cardiac hypertrophy caused by hypertension to heart failure (Iwanaga Y et al.: Circulation 1998; 98:2065). Furthermore, Hasegawa et al. reported that p300, which is an adenovirus E1A binding protein, functioned as a co-activator of GATA-5 (Hasegawa Koji et al.: Blood Pressure vol. 6 1999:665-669). Meanwhile, Kanai et al. confirmed that p300 induced apoptosis in myocardial cells (Presentation, the 63th Annual Scientific Meeting of the Japanese Circulation Society, Mar. 27, 1999-Mar. 29, 1999), and also suggested that there is a possibility that p300 works to suppress cardiac hypertrophy. Thus, the relation between p300 and cardiac hypertrophy is not clear.
Although the onset mechanism of heart failure is gradually being revealed as described above, there are many points which have not sufficiently been unraveled yet. One reason for this lag in the research is the fact that experimental animals to be models of heart failure have not been developed yet.